Predicting Human Dermal Drug Concentrations Using PBPK Modeling and Simulation: Clobetasol Propionate Case Study
AAPS PharmSciTech. 2024 Feb 17;25(3):39. doi: 10.1208/s12249-024-02740-x.ABSTRACTQuantitative in silico tools may be leveraged to mechanistically predict the dermato-pharmacokinetics of compounds delivered from topical and transdermal formulations by integrating systems of rate equations that describe permeation through the formulation and layers of skin and pilo-sebaceous unit, and exchange with systemic circulation via local blood flow. Delivery of clobetasol-17 propionate (CP) from DermovateTM cream was simulated using the Transdermal Compartmental Absorption & Transit (TCATTM) Model in GastroPlus®. The cream was t...
Source: AAPS PharmSciTech - February 17, 2024 Category: Drugs & Pharmacology Authors: William W van Osdol Jasmina Novakovic Maxime Le Merdy Eleftheria Tsakalozou Priyanka Ghosh Jessica Spires Viera Lukacova Source Type: research
Predicting Human Dermal Drug Concentrations Using PBPK Modeling and Simulation: Clobetasol Propionate Case Study
AAPS PharmSciTech. 2024 Feb 17;25(3):39. doi: 10.1208/s12249-024-02740-x.ABSTRACTQuantitative in silico tools may be leveraged to mechanistically predict the dermato-pharmacokinetics of compounds delivered from topical and transdermal formulations by integrating systems of rate equations that describe permeation through the formulation and layers of skin and pilo-sebaceous unit, and exchange with systemic circulation via local blood flow. Delivery of clobetasol-17 propionate (CP) from DermovateTM cream was simulated using the Transdermal Compartmental Absorption & Transit (TCATTM) Model in GastroPlus®. The cream was t...
Source: AAPS PharmSciTech - February 17, 2024 Category: Drugs & Pharmacology Authors: William W van Osdol Jasmina Novakovic Maxime Le Merdy Eleftheria Tsakalozou Priyanka Ghosh Jessica Spires Viera Lukacova Source Type: research
Predicting Human Dermal Drug Concentrations Using PBPK Modeling and Simulation: Clobetasol Propionate Case Study
AAPS PharmSciTech. 2024 Feb 17;25(3):39. doi: 10.1208/s12249-024-02740-x.ABSTRACTQuantitative in silico tools may be leveraged to mechanistically predict the dermato-pharmacokinetics of compounds delivered from topical and transdermal formulations by integrating systems of rate equations that describe permeation through the formulation and layers of skin and pilo-sebaceous unit, and exchange with systemic circulation via local blood flow. Delivery of clobetasol-17 propionate (CP) from DermovateTM cream was simulated using the Transdermal Compartmental Absorption & Transit (TCATTM) Model in GastroPlus®. The cream was t...
Source: AAPS PharmSciTech - February 17, 2024 Category: Drugs & Pharmacology Authors: William W van Osdol Jasmina Novakovic Maxime Le Merdy Eleftheria Tsakalozou Priyanka Ghosh Jessica Spires Viera Lukacova Source Type: research
Predicting Human Dermal Drug Concentrations Using PBPK Modeling and Simulation: Clobetasol Propionate Case Study
AAPS PharmSciTech. 2024 Feb 17;25(3):39. doi: 10.1208/s12249-024-02740-x.ABSTRACTQuantitative in silico tools may be leveraged to mechanistically predict the dermato-pharmacokinetics of compounds delivered from topical and transdermal formulations by integrating systems of rate equations that describe permeation through the formulation and layers of skin and pilo-sebaceous unit, and exchange with systemic circulation via local blood flow. Delivery of clobetasol-17 propionate (CP) from DermovateTM cream was simulated using the Transdermal Compartmental Absorption & Transit (TCATTM) Model in GastroPlus®. The cream was t...
Source: AAPS PharmSciTech - February 17, 2024 Category: Drugs & Pharmacology Authors: William W van Osdol Jasmina Novakovic Maxime Le Merdy Eleftheria Tsakalozou Priyanka Ghosh Jessica Spires Viera Lukacova Source Type: research
Characterization of CYP3A5 Selective Inhibitors for Reaction Phenotyping of Drug Candidates
AbstractCYP3A is one of the most important classes of enzymes and is involved in the metabolism of over 70% drugs. While several selective CYP3A4 inhibitors have been identified, the search for a selective CYP3A5 inhibitor has turned out to be rather challenging. Recently, several selective CYP3A5 inhibitors have been identified through high-throughput screening of ~ 11,000 compounds and hit expansion using human recombinant enzymes. We set forth to characterize the three most selective CYP3A5 inhibitors in a more physiologically relevant system of human liver microsomes to understand if these inhibitors can be used f...
Source: The AAPS Journal - February 16, 2024 Category: Drugs & Pharmacology Source Type: research
A novel three-dimensional Nrf2 reporter epidermis model for skin sensitization assessment
Toxicology. 2024 Feb 8:153743. doi: 10.1016/j.tox.2024.153743. Online ahead of print.ABSTRACTSkin sensitization assessment has progressed from the use of animal models towards the application of New Approach Methodologies (NAMs). Several skin sensitization NAMs are accepted for regulatory use, but a majority relies on submerged in vitro cell cultures that limit their applicability domain, posing challenges for testing hydrophobic chemicals and mixtures. A newly developed three-dimensional (3D) Nrf2 reporter epidermis model for skin sensitization assessment is reported. This NAM may help to overcome these limitations. The N...
Source: Toxicology - February 10, 2024 Category: Toxicology Authors: K Brandmair D Dising D Finkelmeie A Schepky J Kuehnl J Ebmeyea A Burger-Kentischer Source Type: research
Monitoring adherence to vulvar lichen sclerosus treatment - a prospective study
Conclusion: Poor adherence to both twice daily application and prescribed medication quantity occurred frequently. Factors related to self-reported non-adherence included perceived greater efficacy, inconvenience, and time-constraints. Patient adherence to recommended treatment and clinical outcomes are areas for improvement in patients with vulvar lichen sclerosus.PMID:38240095 | DOI:10.1080/09546634.2023.2285725 (Source: Journal of Dermatological Treatment)
Source: Journal of Dermatological Treatment - January 19, 2024 Category: Dermatology Authors: Mallory L Zaino Jessica N Pixley Vani Mangalam Subramanian Deepak Sirdeshmukh Steven R Feldman Rita O Pichardo Source Type: research
Nd:YAG/Er:YAG dual laser compared with topical steroid to treat vulvar lichen sclerosus: A randomised controlled trial
CONCLUSIONS: Non-ablative dual Nd:YAG/Er:YAG laser therapy was safe and significantly improved clinical outcome and subjective symptoms at the 6-month follow up. This suggests that laser may be a promising alternative to corticosteroid therapy. However, the authors caution regular follow ups because of the premalignant nature of the disease.PMID:38149520 | DOI:10.1111/1471-0528.17737 (Source: BJOG : An International Journal of Obstetrics and Gynaecology)
Source: BJOG : An International Journal of Obstetrics and Gynaecology - December 27, 2023 Category: OBGYN Authors: Irena Zivanovic Marianne Gamper Debra Fesslmeier Claudia Walser Sigrid Regauer Volker Viereck Source Type: research
Nd:YAG/Er:YAG dual laser compared with topical steroid to treat vulvar lichen sclerosus: A randomised controlled trial
CONCLUSIONS: Non-ablative dual Nd:YAG/Er:YAG laser therapy was safe and significantly improved clinical outcome and subjective symptoms at the 6-month follow up. This suggests that laser may be a promising alternative to corticosteroid therapy. However, the authors caution regular follow ups because of the premalignant nature of the disease.PMID:38149520 | DOI:10.1111/1471-0528.17737 (Source: BJOG : An International Journal of Obstetrics and Gynaecology)
Source: BJOG : An International Journal of Obstetrics and Gynaecology - December 27, 2023 Category: OBGYN Authors: Irena Zivanovic Marianne Gamper Debra Fesslmeier Claudia Walser Sigrid Regauer Volker Viereck Source Type: research
Nail lichen planus treatment safety
Expert Opin Drug Saf. 2023 Nov 28. doi: 10.1080/14740338.2023.2288902. Online ahead of print.ABSTRACTTopical therapies for nail lichen planus (clobetasol propionate, topical tacrolimus, bath-PUVA), intralesional treatment (triamcinolone), and systemic treatment (corticosteroids, retinoids, small molecule inhibitors (jak/stat inhibitors), TNF-alpha inhibitors (etanercept), systemic immunomodulators (oral calcineurin inhibitors, mycophenolate mophetil), and antimalarials (chloroquine), each with unique safety profiles and considerations. Herein, we discuss common and uncommon adverse events, as well as utilization for specia...
Source: Expert Opinion on Drug Safety - November 28, 2023 Category: Drugs & Pharmacology Authors: Eden N Axler Shari R Lipner Source Type: research
A recalcitrant skin lesion and subsequent infection in a recreational intramural male athlete: a case report
J Athl Train. 2023 Nov 28. doi: 10.4085/1062-6050-0467.22. Online ahead of print.ABSTRACTA 35-year-old intramural male athlete presented to the athletic training staff with a 4.5cm x 2.2cm itchy, painful, swollen, and infected insidious skin lesion on his right lateral malleolus due to an underlying dermatological deficiency. Suspecting infection, the patient was referred to his nurse practitioner and was diagnosed with atopic dermatitis caused by a ceramide deficiency. He was placed on Cefalexin and Mupirocin 2% ointment but returned due to the lesion increasing to 8.5cm x 6cm although infection seemed controlled. He was ...
Source: Journal of Athletic Training - November 28, 2023 Category: Sports Medicine Authors: James E Leone Kimberly A Gray Source Type: research
A recalcitrant skin lesion and subsequent infection in a recreational intramural male athlete: a case report
J Athl Train. 2023 Nov 28. doi: 10.4085/1062-6050-0467.22. Online ahead of print.ABSTRACTA 35-year-old intramural male athlete presented to the athletic training staff with a 4.5cm x 2.2cm itchy, painful, swollen, and infected insidious skin lesion on his right lateral malleolus due to an underlying dermatological deficiency. Suspecting infection, the patient was referred to his nurse practitioner and was diagnosed with atopic dermatitis caused by a ceramide deficiency. He was placed on Cefalexin and Mupirocin 2% ointment but returned due to the lesion increasing to 8.5cm x 6cm although infection seemed controlled. He was ...
Source: J Athl Train - November 28, 2023 Category: Sports Medicine Authors: James E Leone Kimberly A Gray Source Type: research
Nail lichen planus treatment safety
Expert Opin Drug Saf. 2023 Nov 28. doi: 10.1080/14740338.2023.2288902. Online ahead of print.ABSTRACTTopical therapies for nail lichen planus (clobetasol propionate, topical tacrolimus, bath-PUVA), intralesional treatment (triamcinolone), and systemic treatment (corticosteroids, retinoids, small molecule inhibitors (jak/stat inhibitors), TNF-alpha inhibitors (etanercept), systemic immunomodulators (oral calcineurin inhibitors, mycophenolate mophetil), and antimalarials (chloroquine), each with unique safety profiles and considerations. Herein, we discuss common and uncommon adverse events, as well as utilization for specia...
Source: Expert Opinion on Drug Safety - November 28, 2023 Category: Drugs & Pharmacology Authors: Eden N Axler Shari R Lipner Source Type: research
